Standard Montreal Neurological Institute Research Articles

Automatically targeting the dorsolateral subthalamic nucleus for functional connectivity-guided rTMS therapy

Aim: Many resting-state functional magnetic resonance imaging (rs-fMRI) studies have provided evidence that repetitive transcranial magnetic stimulation (rTMS) exerts treatment effects via functional connectivity (FC) from a superficial stimulation target to a deep effective region. The dorsolateral subthalamic nucleus (DL-STN) is an effective target in deep brain stimulation surgery for Parkinson’s disease (PD), but its targeting highly depends on well-trained neurosurgeons and is not easily used for FC-guided rTMS. We aimed to devise a method for automatically localizing the DL-STN, and further develop a one-stop plug-in of rs-fMRI FC analysis to assist future individualized FC-guided rTMS. Methods: Based on structural and iron-sensitive MRI of 78 participants, two raters defined the DL-STN coordinates with very high reliability. The averaged coordinates in the standard Montreal Neurological Institute (MNI) space were: left DL-STN, x: -11.89 ± 0.82, y: -14.51 ± 1.00, and z: -6.40 ± 1.01 and the right DL-STN, x: 12.53 ± 0.77, y: -13.97 ± 0.86, and z: -6.57 ± 0.99. As the individual distances from the averaged coordinates were less than 3 mm (within one voxel for most rs-fMRI studies) for all 78 participants, we defined the average coordinates as AutoSTN. We then developed a one-stop plug-in named Connectivity and Coordinates Converting Assistant Toolbox (CC-CAT) and performed AutoSTN FC analysis. Results: The AutoSTN seed showed significant FC with the motor cortices in all participants. Conclusion: The AutoSTN-based rs-fMRI FC could guide future rTMS on PD. The one-stop plug-in CC-CAT can be used for any FC-guided rTMS treatment.

Specific-CT brain template construction and retrospective dosimetric comparison study in brain for nasopharyngeal carcinoma patients treated with IMRT or VMAT.

The current Radiotherapy (RT) technology still inevitably irradiated normal brain tissue, causing implicit radiation-induced injury. This study investigates the precise localization and the corresponding radiation dosage of brain regions susceptible to damage in nasopharyngeal carcinoma (NPC) patients following RT. Utilizing the Advanced Normalization Tools (ANTs) package, a computed tomography (CT) brain template was created in the standard Montreal Neurological Institute (MNI) space, based on 803 Chinese NPC patients (T0~T4) who underwent RT. With this template, all patients' CT and RTdose data were registered to the MNI space, and the RTdose distribution characteristics in normal brain tissues were compared for NPC patients treated with Intensity-modulated radiotherapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT), with patients' age and gender as covariates. Analysis of the average dosages indicated that certain areas within the Limbic, Temporal, and Posterior Lobes, the Brainstem, and the Cerebellum Posterior Lobe were exposed to doses exceeding 50 Gy. Inter-group analysis revealed that IMRT delivered higher doses than VMAT to brain regions anterior to the nasopharyngeal tumor, whereas VMAT affected the posterior regions more. Interestingly, VMAT showed a drawback in preserving the normal brain tissues for T4-stage patients. This revealed that the two treatment modalities have unique characteristics in preserving normal brain tissue, each with advantages. With better localization precision, the created CT brain template in MNI space may be beneficial for NPC patients' toxicity and dosimetric analyses.

Neuroanatomical mapping of inhibitory attention and working memory with functional magnetic resonance imaging in healthy children

The objective is to produce an average brain activation mapping template in healthy children using functional magnetic resonance imaging (fMRI), with specific paradigms for activating inhibitory attention and working memory functions. A nutritional and neuropsychological evaluation was performed on 87 right-handed children. The inclusion criteria were met by 30 children (15 boys and 15 girls) between 9 and 11 years old, who were studied with fMRI in two inhibitory attention tests (Go/No Go), with food cues, a working memory test (Continuous Performance Test Identical Pairs) and measurement of anatomical volumes. These data were subsequently processed with the FSL-v5 program, with a threshold of p < 0.05 (cluster-wise). The brain areas activated were located using a standard Montreal Neurological Institute brain template and the Harvard-Oxford structural cortical atlas. The inhibitory attention tests showed activation frontal areas predominantly on the right, and the cingulate, parietal and occipital areas, with preponderance in occipital areas in the food cues test. In the Continuous Performance Test-Identical Pairs test, activation was obtained predominantly in the occipital, frontal and parietal areas. Brain activity mapping templates are obtained in healthy children with tests for inhibitory attention, food cues and working memory. The activation areas are mostly those reported in the literature. This provides baseline brain activation patterns for studying pathologies related to inhibitory attention, impulsivity and working memory.

Deep brain stimulation for Tourette syndrome: modulation of the limbic-motor interface network.

Deep brain stimulation (DBS) is an effective treatment for medically refractory Tourette syndrome (TS). Several effective targets have been reported, but there is still controversy about the networks involved in the efficacy of DBS for TS. Here, the authors aimed to identify the basal ganglia-thalamo-cortical networks associated with tic and obsessive-compulsive behavior (OCB) improvement and the network link between the two main targets for TS. A retrospective analysis of 21 patients treated with pallidal and thalamic DBS was performed. Tics and OCB scores were recorded before and after DBS. The authors localized the electrodes in standard MNI (Montreal Neurological Institute) space and calculated the volume of tissue activated with the settings at the last follow-up to obtain areas of maximal improvement ("sweet spots") among all patients for the pallidal and thalamic targets. Tractography was used to show the white matter pathways associated with maximal tic and OCB improvement. Ten patients treated with pallidal DBS and 11 patients treated with thalamic DBS were included. Responder rates were 80% in the pallidal and 64% in the thalamic target groups. Sweet spots for tics and OCB clustered in several areas across the basal ganglia and thalamus delineated two main networks. Tic reduction in the pallidal target mapped to a limbic pallidothalamic network and in the thalamic target to the premotor thalamocortical network. Putting these two networks together will form the main output of the so-called limbic-motor interface network. However, OCB reduction mapped a dorsomedial prefrontal cortex/dorsal anterior cingulate (dmPFC/dACC) network. The authors demonstrated the involvement of the limbic-motor interface network during effective DBS for tics in patients with TS. OCB redution was associated with the additional involvement of dmPFC/dACC connections passing dorsal to the head of the globus pallidus pars externa on its way to the thalamus and midbrain.

A detailed dosimetric comparative study of IMRT and VMAT in normal brain tissues for nasopharyngeal carcinoma patients treated with radiotherapy.

Radiotherapy (RT) is the primary treatment for nasopharyngeal carcinoma (NPC). However, it can cause implicit RT-induced injury by irradiating normal brain tissue. To date, there have been no detailed reports on the radiated exact location in the brain, the corresponding radiation dose, and their relationship. We analyzed 803 Chinese NPC patients treated with RT and used a CT brain template in a Montreal Neurological Institute (MNI) space to compare the group differences in RT dose distribution for different RT technologies (IMRT or VMAT). Brain regions that received high doses (>50 Gy) of radiation were mainly located in parts of the temporal and limbic lobes, where radioactive damage often occurs. Brain regions that accepted higher doses with IMRT were mainly located near the anterior region of the nasopharyngeal tumor, while brain regions that accepted higher doses with VMAT were mainly located near the posterior region of the tumor. No significant difference was detected between IMRT and VMAT for T1 stage patients. For T2 stage patients, differences were widely distributed, with VMAT showing a significant dose advantage in protecting the normal brain tissue. For T3 stage patients, VMAT showed an advantage in the superior temporal gyrus and limbic lobe, while IMRT showed an advantage in the posterior cerebellum. For T4 stage patients, VMAT showed a disadvantage in protecting the normal brain tissue. These results indicate that IMRT and VMAT have their own advantages in sparing different organs at risk (OARs) in the brain for different T stages of NPC patients treated with RT. Our approach for analyzing dosimetric characteristics in a standard MNI space for Chinese NPC patients provides greater convenience in toxicity and dosimetry analysis with superior localization accuracy. Using this method, we found interesting differences from previous reports: VMAT showed a disadvantage in protecting the normal brain tissue for T4 stage NPC patients.

Stages of tau aggregation associated with amyloidosis reflected in non‐negative matrix factorization components

AbstractBackgroundTau aggregation, when accompanied by amyloid deposition, is a key neuropathological signature of Alzheimer’s disease (AD). The regional distribution of tau may be a more sensitive marker of AD pathology than total tau level, however the spread of disease is unlikely to conform to common atlas‐based regions of interest. As such, methods for evaluating tau’s regional distribution could be useful for predicting AD staging or disease progression. In this analysis, we derive regional patterns of tau aggregation in AD using nonnegative matrix factorization (NNMF), a data‐driven method of identifying areas of the brain that consistently covary across individuals.MethodWe used data from 269 ‐amyloid (A) positive subjects with 18F‐flortaucipir‐PET data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database and the AVID study (138 females, mean age = 73.09; 110 healthy controls, 118 MCI, and 41 AD). PET data were registered to Standard Montreal Neurological Institute (MNI152) 182x218x182 grid with 1mm resolution. SUVR maps were computed with a cerebellar gray matter reference and NNMF was used to estimate common patterns of tau aggregation. Once these patterns were identified, mean SUVR for each component computed for each participant. We performed Gaussian mixture modeling for each component to determine optimal tau positivity cutpoint, and subjects were classified as positive or negative for each component. Components were ordered by frequency of appearance in subjects in order to determine staging.Result12 regional patterns of tau binding were identified (Figure 1). The patterns most commonly expressed among subjects reflected regions of the temporal lobe (Figure 2a). This was particularly noted in those with AD (Figure 2b). These components were followed by a component including the lingual gyrus, and then by components involving frontal lobes, precuneus, and parietal lobes.ConclusionNNMF‐derived tau PET components provide a data‐driven method for identifying common patterns of tau aggregation, producing stages that are consistent with previous research on tau pathology in AD. These components may provide a more sensitive method for identifying disease progression in AD.

Functional architecture of the motor homunculus detected by electrostimulation.

We performed a prospective electrostimulation study of the motor homunculus in 100 patients without motor deficit or brain lesion in the precentral gyrus in order to acquire accurate Montreal Neurological Institute (MNI) coordinates of the functional areas. The analysis of 248 body coordinates in the precentral gyrus showed rare inter-individual variations in the medial-to-lateral somatotopic movement organization with quite similar intensity thresholds. Electrostimulation only induced basic and stereotyped movements. We detected a relative medial-to-lateral somatotopy of the wrist/hand/global/individual fingers, with sometimes different sites for an individual muscle or movement. We found some similarities to, but also substantial differences from, the seminal work of Penfield and colleagues. We propose an updated version of the human motor homunculus and of its correlation with the somatosensory homunculus, previously defined in MNI space with a similar brain mapping technique. In this prospective electrostimulation study, based on 100 operated patients without motor deficit or brain lesion in the precentral gyrus, we acquired coordinates of the functional areas of the motor homunculus and normalized them to standard MNI space. Among 608 sites stimulated in the precentral gyrus (and 1937 in gyri nearby), 248 positive points (40%) for motor response were detected - 245 in the precentral gyrus. Positive stimulations were detected through the 'on/off' outbreak effect, and only basic movements were detected. We found no significant difference in mean intensity threshold between the motor representations of the fingers (1.94mA), tongue and lower limbs (both 2.0mA), or face (2.25mA). In the precentral gyrus, the evoked body movements displayed a medial-to-lateral somatotopy in very small (often <10mm2 ) areas. The hand region displayed multiple areas for a specific movement, with areas inducing either global or single-finger movement (with a relative medial-to-lateral somatotopy). Among these tested patients, the somatotopic organization of the intact motor cortex showed little inter-individual variations. Unlike Penfield and collaborators, we evoked no sensations such as sense of movement or desire to move, and only 2% of motor responses outside the precentral gyrus. We propose a rationalization of the standard drawing of the motor homunculus according to MNI space. We found a somatotopic correlation perpendicular to the central sulcus when matching our motor data to those previously obtained for the somatosensory homunculus.

Early Detection of Alzheimer's Disease Using Magnetic Resonance Imaging: A Novel Approach Combining Convolutional Neural Networks and Ensemble Learning.

Early detection is critical for effective management of Alzheimer’s disease (AD) and screening for mild cognitive impairment (MCI) is common practice. Among several deep-learning techniques that have been applied to assessing structural brain changes on magnetic resonance imaging (MRI), convolutional neural network (CNN) has gained popularity due to its superb efficiency in automated feature learning with the use of a variety of multilayer perceptrons. Meanwhile, ensemble learning (EL) has shown to be beneficial in the robustness of learning-system performance via integrating multiple models. Here, we proposed a classifier ensemble developed by combining CNN and EL, i.e., the CNN-EL approach, to identify subjects with MCI or AD using MRI: i.e., classification between (1) AD and healthy cognition (HC), (2) MCIc (MCI patients who will convert to AD) and HC, and (3) MCIc and MCInc (MCI patients who will not convert to AD). For each binary classification task, a large number of CNN models were trained applying a set of sagittal, coronal, or transverse MRI slices; these CNN models were then integrated into a single ensemble. Performance of the ensemble was evaluated using stratified fivefold cross-validation method for 10 times. The number of the intersection points determined by the most discriminable slices separating two classes in a binary classification task among the sagittal, coronal, and transverse slice sets, transformed into the standard Montreal Neurological Institute (MNI) space, acted as an indicator to assess the ability of a brain region in which the points were located to classify AD. Thus, the brain regions with most intersection points were considered as those mostly contributing to the early diagnosis of AD. The result revealed an accuracy rate of 0.84 ± 0.05, 0.79 ± 0.04, and 0.62 ± 0.06, respectively, for classifying AD vs. HC, MCIc vs. HC, and MCIc vs. MCInc, comparable to previous reports and a 3D deep learning approach (3D-SENet) based on a more state-of-the-art and popular Squeeze-and-Excitation Networks model using channel attention mechanism. Notably, the intersection points accurately located the medial temporal lobe and several other structures of the limbic system, i.e., brain regions known to be struck early in AD. More interestingly, the classifiers disclosed multiple patterned MRI changes in the brain in AD and MCIc, involving these key regions. These results suggest that as a data-driven method, the combined CNN and EL approach can locate the most discriminable brain regions indicated by the trained ensemble model while the generalization ability of the ensemble model was maximized to successfully capture AD-related brain variations early in the disease process; it can also provide new insights into understanding the complex heterogeneity of whole-brain MRI changes in AD. Further research is needed to examine the clinical implication of the finding, capability of the advocated CNN-EL approach to help understand and evaluate an individual subject’s disease status, symptom burden and progress, and the generalizability of the advocated CNN-EL approach to locate the most discriminable brain regions in the detection of other brain disorders such as schizophrenia, autism, and severe depression, in a data-driven way.

Identification of acute intracranial bleed on computed tomography using computer aided detection

Intracranial haemorrhage can be life threatening. Timely detection of acute intracranial haemorrhage in an emergency room is essential so that the patient can be given medical attention without delay. This has led to the use of Computer Aided Detection (CAD) systems which can help to pick up and prioritize patients with high risk of bleeding. A CAD for identification of acute intracranial haemorrhage in Computed Tomography (CT) on a per patient basis was developed in this project. The CAD is aimed to be a triage tool which determines the priority of image being read by radiologists. It was developed and validated using 119 and 108 volumes of brain CT images respectively. The volumes were first registered to standard Montreal Neurological Institute (MNI) space. Slices close to the base and top of the skull that tend to contribute to false positives were omitted. Then, the volumes were analysed by a fully automated CAD program developed in MATLAB. The algorithm involved multiple thresholding and symmetry detection in 3D to detect acute intracranial haemorrhage. The evaluation took around 5s per volume. On a per patient basis, the CAD achieved sensitivity of 75.0%, specificity of 83.8%, and accuracy of 80.6% in the validation set.

Cortical Excitability through Anodal Transcranial Direct Current Stimulation: a Computational Approach.

The present study analyzes the effect of various anodal transcranial direct current stimulation (tDCS) configurations in terms of electric field and voltage distribution. The work aims to assess the role of tDCS configurations considering subject's specific anatomy in a computational framework. The study considers the effect of conventional and high definition transcranial direct current stimulation (HD-tDCS) by using synthetic magnetic resonance image (MRI) volumes for normal brain and brain with multiple sclerosis (MS) lesions. The configurations presented in this study compare the effect of various m x n HD-tDCS and conventional tDCS on standard Montreal Neurological Institute (MNI152) head model which is a T1 MRI volume obtained by averaging 152 individuals at 1mm3 resolution. The study evaluates the role of disc, ring, and pad electrodes in various configurations of tDCS application. The approximate surface area for each electrode in HD-tDCS application considered in the study is 113mm2. The significant difference in voltage distribution has been observed due to 1 × 1 HD-tDCS configuration on synthetic MRI of normal and lesion brain using disc and ring electrodes. For region specific approach, outer ring structured electrode configuration - an extended m x n HD-tDCS configuration is presented in this study. The proposed outer ring HD-tDCS configuration has been compared with m × 1 and m × 2 HD-tDCS configurations with different types of electrodes in terms of focality, induced electric field and voltage generated. On the basis of the insights gained from the analysis of various tDCS configurations on standard, normal and lesion structural data, the design of HD-tDCS as a tool in neuro-rehabilitation has been proposed. This computational model approach is useful in fixing various parameters of current stimulation: intensity, type and arrangement of electrodes and target region by using structural MRI data of an individual prior to the real stimulation in clinical trials.

92Transcatheter aortic valve implantation improves cerebral blood flow and cognitive function in elderly patients with aortic stenosis - Brain perfusion SPECT imaging study

Abstract Background Cognitive impairment and depression are commonly noted in elderly frail patients with severe aortic stenosis (AS). However, their mechanisms and reversibility after treatment remain remain to be examined. Purpose In this study, we examined whether transcatheter aortic valve implantation (TAVI) increases cerebral blood flow (CBF) in cognitive/emotional brain areas, such as the hippocampus, in the elderly patients with severe AS. Methods We examined consecutive 15 right-handed patients with severe AS who were eligible for TAVI (median age 83.2 years, 12 (80%) women). We evaluated the following assessments both at baseline and 3 months after TAVI. Frailty was evaluated based on Fried scale, which consists of 5 items, including gait speed, cognitive function, weight loss, exhaustion, and inactivity. Frail and pre-frail were defined as greater than 3 and 1∼2 in the scale, respectively. Cognitive and emotional status were evaluated with Logical Memory (LM) II, Mini Mental State Examination (MMSE), and geriatric depression scale (GDS). Lower LM II (less than 4 points) and MMSE (less than 24 points) and higher GDS (more than 6 points) indicate worse memory, general cognitive function, and depressive symptoms, respectively. CBF images were recorded with 99mTc single-photon emission computed tomography and were analyzed using SPM12. Briefly, CBF images were firstly normalized to the standard Montreal Neurological Institute space. Then, a voxel-wise parametric analysis was conducted between normalized CBF images at baseline and those after TAVI (P&lt;0.005 at each voxel). Continuous variables were presented as mean ± standard error (SE). Normality was assessed using the Shapiro-Wilk test. Continuous variables were compared with the use of paired t test. Linear mixed-model analysis was performed to evaluate changes in neuropsychological tests and CBF over time. Results In the present study, all patients were not robust but pre-frail (47.3%) or frail (53.7%). LM II score was significantly improved at 3 months after TAVI compared with baseline (baseline, 8.7 vs. 3 months, 13.8, P&lt;0.01) (Figure A), whereas no significant changes in MMSE or GDS scores were noted (baseline, 24.6 vs. 3 months, 25.2 for MMSE; baseline, 4.3 vs. 3 months, 4.2 for GDS). Importantly, although no patients showed clinical symptoms or signs for transient ischemic attack or stroke after TAVI, CBF in the local regions, including the right hippocampus, was significantly increased after TAVI compared with baseline (P&lt;0.005 at each voxel) (green arrowheads) (Figure B). Furthermore, CBF in the right hippocampus were positively correlated with LM II scores (P=0.017) (Figure C). Figure 1 Conclusions These results provide the first evidence that TAVI improves cerebral perfusion (especially that in the hippocampus) and cognitive functions in elderly patients with severe AS.

Voxel-wise radiogenomic mapping of tumor location with key molecular alterations in patients with glioma.

This study aims to evaluate the impact of tumor location on key molecular alterations on a single voxel level in patients with newly diagnosed glioma. A consecutive series of n = 237 patients with newly diagnosed glioblastoma and n = 131 patients with lower-grade glioma was analyzed. Volumetric tumor segmentation was performed on preoperative MRI with a semi-automated approach and images were registered to the standard Montreal Neurological Institute 152 space. Using a voxel-based lesion symptom mapping (VLSM) analysis, we identified specific brain regions that were associated with tumor-specific molecular alterations. We assessed a predefined set of n = 17 molecular characteristics in the glioblastoma cohort and n = 2 molecular characteristics in the lower-grade glioma cohort. Permutation adjustment (n = 1000 iterations) was used to correct for multiple testing, and voxel t-values that were greater than the t-value in >95% of the permutations were retained in the VLSM results (α = 0.05, power > 0.8). Tumor location predilection for isocitrate dehydrogenase (IDH) mutant tumors was found in both glioblastoma and lower-grade glioma cohorts, each showing a concordant predominance in the frontal lobe adjacent to the rostral extension of the lateral ventricles (permutation-adjusted P = 0.021 for the glioblastoma and 0.013 for the lower-grade glioma cohort). Apart from that, the VLSM analysis did not reveal a significant association of the tumor location with any other key molecular alteration in both cohorts (permutation-adjusted P > 0.05 each). Our study highlights the unique properties of IDH mutations and underpins the hypothesis that the rostral extension of the lateral ventricles is a potential location for the cell of origin in IDH-mutant gliomas.

Population differences in brain morphology: Need for population specific brain template

Brain templates provide a standard anatomical platform for population based morphometric assessments. Typically, standard brain templates for such assessments are created using Caucasian brains, which may not be ideal to analyze brains from other ethnicities. To effectively demonstrate this, we compared brain morphometric differences between T1 weighted structural MRI images of 27 healthy Indian and Caucasian subjects of similar age and same sex ratio. Furthermore, a population specific brain template was created from MRI images of healthy Indian subjects and compared with standard Montreal Neurological Institute (MNI-152) template. We also examined the accuracy of registration of by acquiring a different T1 weighted MRI data set and registering them to newly created Indian template and MNI-152 template. The statistical analysis indicates significant difference in global brain measures and regional brain structures of Indian and Caucasian subjects. Specifically, the global brain measurements of the Indian brain template were smaller than that of the MNI template. Also, Indian brain images were better realigned to the newly created template than to the MNI-152 template. The notable variations in Indian and Caucasian brains convey the need to build a population specific Indian brain template and atlas.

Feasibility of Magnetoencephalography after Endovascular Treatment of Ruptured Intracranial Aneurysms.

Among good outcome survivors of aneurysmal subarachnoid hemorrhage (aSAH), only 23% have normal neurocognitive performance, despite imaging that is often normal. The aim of this work is to explore the use of magnetoencephalography (MEG) after endovascular treatment of ruptured aneurysms. Good outcome aSAH patients treated with coiling and matched controls were recruited. Clinical assessments and resting-state MEG and anatomical MRI images were obtained. Brain space was normalized to standard Montreal Neurological Institute (MNI) brain. Areas of interest were identified with Automated Anatomical Labeling (AAL) and "electrodes" reconstructed using vector beamformer. Spectral power density estimates for each location was averaged across the brain to derive mean signal power. Virtual-sensor data closest to the coil was assessed for signal quality. Thirteen aSAH patients and 13 matched controls were recruited. Mean age was 54.5 years (SD = 9.9) for controls and 56.8 years (SD = 11.8) for aSAH. The majority of aneurysms (62%) were in the midline. Mean time from aSAH to MEG was 18.8 months (2.4-67.5; SD = 19). Data quality was comparable in both groups, including the virtual-sensors close to the coil mass. Mean signal power showed no significant spectral alterations in the aSAH group. MEG is feasible in aSAH patients after endovascular treatment. Our results suggest that the signal quality and strength is good, and the presence of coils does not interfere with testing. Considering the common neurocognitive complaints of aSAH survivors MEG could be developed to diagnose, quantify, and monitor neurocognitive problems after aSAH.

Automated PET-only quantification of amyloid deposition with adaptive template and empirically pre-defined ROI

Amyloid PET is useful for early and/or differential diagnosis of Alzheimer’s disease (AD). Quantification of amyloid deposition using PET has been employed to improve diagnosis and to monitor AD therapy, particularly in research. Although MRI is often used for segmentation of gray matter and for spatial normalization into standard Montreal Neurological Institute (MNI) space where region-of-interest (ROI) template is defined, 3D MRI is not always available in clinical practice. The purpose of this study was to examine the feasibility of PET-only amyloid quantification with an adaptive template and a pre-defined standard ROI template that has been empirically generated from typical cases. A total of 68 subjects who underwent brain 11C-PiB PET were examined. The 11C-PiB images were non-linearly spatially normalized to the standard MNI T1 atlas using the same transformation parameters of MRI-based normalization. The automatic-anatomical-labeling-ROI (AAL-ROI) template was applied to the PET images. All voxel values were normalized by the mean value of cerebellar cortex to generate the SUVR-scaled images. Eleven typical positive images and eight typical negative images were normalized and averaged, respectively, and were used as the positive and negative template. Positive and negative masks which consist of voxels with SUVR ⩾1.7 were extracted from both templates. Empirical PiB-prone ROI (EPP-ROI) was generated by subtracting the negative mask from the positive mask. The 11C-PiB image of each subject was non-rigidly normalized to the positive and negative template, respectively, and the one with higher cross-correlation was adopted. The EPP-ROI was then inversely transformed to individual PET images. We evaluated differences of SUVR between standard MRI-based method and PET-only method. We additionally evaluated whether the PET-only method would correctly categorize 11C-PiB scans as positive or negative. Significant correlation was observed between the SUVRs obtained with AAL-ROI and those with EPP-ROI when MRI-based normalization was used, the latter providing higher SUVR. When EPP-ROI was used, MRI-based method and PET-only method provided almost identical SUVR. All 11C-PiB scans were correctly categorized into positive and negative using a cutoff value of 1.7 as compared to visual interpretation. The 11C-PiB SUVR were 2.30 ± 0.24 and 1.25 ± 0.11 for the positive and negative images. PET-only amyloid quantification method with adaptive templates and EPP-ROI can provide accurate, robust and simple amyloid quantification without MRI.

Building a FP-CIT SPECT Brain Template Using a Posterization Approach.

Spatial affine registration of brain images to a common template is usually performed as a preprocessing step in intersubject and intrasubject comparison studies, computer-aided diagnosis, region of interest selection and brain segmentation in tomography. Nevertheless, it is not straightforward to build a template of [123I]FP-CIT SPECT brain images because they exhibit very low intensity values outside the striatum. In this work, we present a procedure to automatically build a [123I]FP-CIT SPECT template in the standard Montreal Neurological Institute (MNI) space. The proposed methodology consists of a head voxel selection using the Otsu's method, followed by a posterization of the source images to three different levels: background, head, and striatum. Analogously, we also design a posterized version of a brain image in the MNI space; subsequently, we perform a spatial affine registration of the posterized source images to this image. The intensity of the transformed images is normalized linearly, assuming that the histogram of the intensity values follows an alpha-stable distribution. Lastly, we build the [123I]FP-CIT SPECT template by means of the transformed and normalized images. The proposed methodology is a fully automatic procedure that has been shown to work accurately even when a high-resolution magnetic resonance image for each subject is not available.

Lead-DBS: A toolbox for deep brain stimulation electrode localizations and visualizations

To determine placement of electrodes after deep brain stimulation (DBS) surgery, a novel toolbox that facilitates both reconstruction of the lead electrode trajectory and the contact placement is introduced. Using the toolbox, electrode placement can be reconstructed and visualized based on the electrode-induced artifacts on post-operative magnetic resonance (MR) or computed tomography (CT) images.Correct electrode placement is essential for efficacious treatment with DBS. Post-operative knowledge about the placement of DBS electrode contacts and trajectories is a promising tool for clinical evaluation of DBS effects and adverse effects. It may help clinicians in identifying the best stimulation contacts based on anatomical target areas and may even shorten test stimulation protocols in the future.Fifty patients that underwent DBS surgery were analyzed in this study. After normalizing the post-operative MR/CT volumes into standard Montreal Neurological Institute (MNI)-stereotactic space, electrode leads (n=104) were detected by a novel algorithm that iteratively thresholds each axial slice and isolates the centroids of the electrode artifacts within the MR/CT-images (MR only n=32, CT only n=10, MR and CT n=8). Two patients received four, the others received two quadripolar DBS leads bilaterally, summing up to a total of 120 lead localizations. In a second reconstruction step, electrode contacts along the lead trajectories were reconstructed by using templates of electrode tips that had been manually created beforehand. Reconstructions that were made by the algorithm were finally compared to manual surveys of contact localizations.The algorithm was able to robustly accomplish lead reconstructions in an automated manner in 98% of electrodes and contact reconstructions in 69% of electrodes. Using additional subsequent manual refinement of the reconstructed contact positions, 118 of 120 electrode lead and contact reconstructions could be localized using the toolbox.Taken together, the toolbox presented here allows for a precise and fast reconstruction of DBS contacts by proposing a semi-automated procedure. Reconstruction results can be directly exported to two- and three-dimensional views that show the relationship between DBS contacts and anatomical target regions. The toolbox is made available to the public in form of an open-source MATLAB repository.

Postoperative MRI localisation of electrodes and clinical efficacy of pallidal deep brain stimulation in cervical dystonia

IntroductionPallidal deep brain stimulation (DBS) has been shown to be effective in cervical dystonia (CD) with an improvement of about 50–60% in the Toronto Western Spasmodic Torticollis Rating (TWSTR) Scale....

Probabilistic map of critical functional regions of the human cerebral cortex: Broca's area revisited.

The organization of basic functions of the human brain, particularly in the right hemisphere, remains poorly understood. Recent advances in functional neuroimaging have improved our understanding of cortical organization but do not allow for direct interrogation or determination of essential (versus participatory) cortical regions. Direct cortical stimulation represents a unique opportunity to provide novel insights into the functional distribution of critical epicentres. Direct cortical stimulation (bipolar, 60 Hz, 1-ms pulse) was performed in 165 consecutive patients undergoing awake mapping for resection of low-grade gliomas. Tasks included motor, sensory, counting, and picture naming. Stimulation sites eliciting positive (sensory/motor) or negative (speech arrest, dysarthria, anomia, phonological and semantic paraphasias) findings were recorded and mapped onto a standard Montreal Neurological Institute brain atlas. Montreal Neurological Institute-space functional data were subjected to cluster analysis algorithms (K-means, partition around medioids, hierarchical Ward) to elucidate crucial network epicentres. Sensorimotor function was observed in the pre/post-central gyri as expected. Articulation epicentres were also found within the pre/post-central gyri. However, speech arrest localized to ventral premotor cortex, not the classical Broca's area. Anomia/paraphasia data demonstrated foci not only within classical Wernicke's area but also within the middle and inferior frontal gyri. We report the first bilateral probabilistic map for crucial cortical epicentres of human brain functions in the right and left hemispheres, including sensory, motor, and language (speech, articulation, phonology and semantics). These data challenge classical theories of brain organization (e.g. Broca's area as speech output region) and provide a distributed framework for future studies of neural networks.

White matter microstructural abnormalities in patients with late-onset schizophrenia identified by a voxel-based diffusion tensor imaging

Reduced fractional anisotropy (FA) has been previously found in diffusion tensor imaging (DTI) studies of white matter in schizophrenic patients. However, there are no reports in the literature that address FA alterations in late-onset schizophrenia (LOS). The current study measured FA in whole white matter and subsequently analyzed its association with psychotic symptoms in LOS. DTI was carried out in 20 patients with LOS and 17 age-, gender- and education-matched healthy subjects. Fractional anisotropy in different areas of white matter was compared between groups using a voxelwise analysis after inter-subject registration to standard Montreal Neurological Institute (MNI) space. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Cognitive functions were measured using the Wisconsin Card Sorting Test (WCST), the Digit Span Test, and the Trail-making Test. Significant reduction in FA was found in the left parietal lobe and right posterior cingulum in LOS patients compared with healthy subjects. Significant deficits in cognitive functions were observed in LOS. No significant correlation was found between FA value and PANSS scores, cognitive test scores, age, or antipsychotic medication dosages in LOS patients. Our study suggests that abnormalities in white matter integrity may contribute to the pathophysiology of LOS. However, these microstructural abnormalities provided no evidence for the emergence of psychotic symptoms in LOS.